肠道微生物转位与抗病毒治疗后HIV感染者γδ T细胞活化的关系

Association between microbial translocation and γδ T cell activation in HIV-infected patients under antiretroviral therapy

目的评价抗逆转录病毒治疗(antiretroviral therapy,ART)后人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者免疫活化水平与微生物转位的关系。方法分别选取2017年1月至2017年12月在首都医科大学附属北京佑安医院接受ART的27例HIV感染者和27例健康对照为研究对象。用ELISA法检测血浆中脂多糖(LPS)、LPS结合蛋白(LBP)和可溶性CD14(sCD14)的水平;用流式细胞术检测γδT细胞表面CD38和HLA-DR分子的表达。结果 ART后HIV感染者血浆中LBP和sCD14的水平较健康对照组均显著增加[(51.50±13.82)μg/ml vs(37.40±18.63)μg/ml,P=0.039;(1.75±0.31)μg/ml vs(1.36±0.25)μg/ml,P=0.008],而血浆中LPS水平与健康对照组比较,差异无统计学意义[(11.16±14.24)EU/ml vs(5.53±5.08)EU/ml,P=0.099]。此外,与健康对照组比较,ART后HIV感染者CD38^+γδT细胞、HLA-DR^+γδT细胞和CD38^+HLA-DR^+γδT细胞的比例均显著增加[(40.56±16.80)%vs(59.98±20.90)%,P=0.003;(37.63±17.47)%vs(54.95±14.69)%,P=0.002;(18.51±11.49)%vs(35.86±17.06)%,P=0.001]。然而,血浆LPS、LBP和sCD14的水平与CD38^+γδT细胞、HLA-DR^+γδT细胞和CD38^+HLA-DR^+γδT细胞的比例间无显著相关性(P均>0.05)。结论 ART后,HIV感染者γδT细胞的活化水平仍然增高,而γδT细胞的活化与肠道微生物转位无关。

Objective To study the associations between microbial translocation andγδT cell activation in human immunodeficiency virus(HIV)- infected patients under antiretroviral therapy(ART). Methods ARTtreated HIV-infected patients(n=27)and healthy controls(n=27)during January 2017to December 2017 were enrolled in this study.The plasma levels of lipopolysaccharide(LPS),LPS binding protein(LBP)and soluble CD14(sCD14)were measured by ELISA;the expression of CD38and HLA-DR onγδT cell was performed by flow cytometry. Results The plasma levels of LBP and sCD14were significantly increased in ART-treated HIV-infected patients comparing to that of healthy controls [(51.50±13.82)μg/ml vs(37.40 ±18.63)μg/ml,P=0.039;(1.75±0.31)μg/ml vs (1.36±0.25)μg/ml,P=0.008].However,there was no significant difference of the plasma levels of LPS between ART-treated HIV-infected patients and healthy controls.Moreover,compared with healthy controls,the frequencies of CD38^+γδT cell,HLA-DR^+γδ T cell and CD38+HLA-DR+γδT cell were significantly increased [(40.56±16.80)%vs(59.98±20.90)%, P=0.003;(37.63±17.47)%vs(54.95±14.69)%,P=0.002;(18.51±11.49)%vs(35.86±17.06)%, P=0.001].However,there were no correlations between the levels of LPS,LBP and sCD14and the frequencies of CD38^+γδT cell,HLA-DR^+γδT cell and CD38^+HLA-DR^+γδT cell. Conclusions γδT cells persist highly activated in ART-treated HIV-infected patients,and gut microbial translocation cannot directly driveγδT cell activation.